MBD - Biochemistry Flashcards

Question

What do PTH and FGF-23 cause in regards to PO43-?

Answer 1

PTH • PO43- LOSS FGF-23 • PO43- LOSS • Inhibits CALCITRIOL formation

Answer 2

FGF-23 and PTH inhibit the phosphate/Na co-transporters and so result in phosphate loss: o FGF-23 inhibits NPT2a and NPT2c. o PTH inhibits NPT2a  Phosphate is fully filtered and only reabsorbed in the PCT.  FGF-23 is produced by osteoblasts and causes phosphate loss BUT also INHIBITS activation of VitD by 1-alpha-hydroxylase

Answer 3

 Calcium and phosphate is reabsorbed and then PTH secretion is switched off due to high [Ca] –ve feedback.  Osteoblasts produces FGF-23 to switch off phosphate reabsorption (as phosphate higher too) but FGF-23 also switches off calcitriol formation.  FGF-23 INHBITS calcitriol formation. o THIS IS HOW IT ALSO LEADS TO OSTEOMALACIA.

Answer 4

Due to FGF-23, can also get renal PO43- loss when [Ca] & [VitD] levels are NORMAL Called 'Isolated' Hypophosphatemia: o X-linked hypophosphatemia Rickets o Autosomal dominant hypophosphatemia rickets (ADRR) o Oncogenic osteomalacia All 3 of these lead to HIGH FGF-23 Kidney PCT damage can lead to hypophosphatemia & phosphaturia

Answer 5

Low bone density! High turnover • increased bone resorption >> bone formation • e.g. oestrogen deficiency Low turnover • decreased bone formation >> bone resorption • e.g. liver disease Increase bone resorption & decreased bone formation • e.g. glucocorticoids

Answer 6

o Increased number of remodelling units o Causes remodelling imbalance – increased resorption compared to formation o Remodelling errors (deeper and more resorption pits) lead to trabecular perforation and cortical excess excavation o Decreased osteocyte sensing.

Answer 7

 Cancellous bone loss is marked EARLY in the menopause  Osteoporosis results in increased fracture risks.

Answer 8

Used to EXCLUDE other causes • serum biochemistry should be NORMAL if osteoporosis  Check for VitD deficiency.  Check for 2o endocrine causes – e.g. P-HPT (PTH high), P-HT (T3 high), hypogonadism.  Exclude multiple myeloma.  Check for high urine calcium

Answer 9

Bone Density - BMD • represents 70% of total risk  DEXA scans – measures differences in densities between 2 different materials  Definition of osteoporosis is based on BMD – T-score: <=-2.5 = osteoporosis. • 1 S.D. reduction = 2.5x increase in fracture risk. We measure: • vertebral (commonest fractures, measures cancellous bone which is metabolic bone so responds fastest to treatment) AND • hip (second most common) BMDs  FRAX – Fracture Risk Assessment Tool – uses BMD (Ludley for equation!!)

Answer 10

BONE MARKERS! Unlike BMD, bone markers are DYNAMIC  Formation markers: • P1NP – Procollagen type 1 N-terminal Propeptide  In production of collagen (2112), extension polypeptides (P1NP) are cleaved ```  Resorption markers: • Serum CTX – Cross-linked C-telopeptides. • Urine NTX – Cross-linked N-telopeptides  3 hydroxylysine molecules condense out to form a pyridinium ring linkage on resorption of bone ```

Answer 11

Resorption markers!! Monitoring response to treatment with anti-resorptive drugs: o Bone reabsorption markers fall in 4-6 weeks o Expect a 50% drop of urine NTx by 3 months ``` Problems though with cross-links:  Hard to reproduce.  Positive association with age anyway.  Need to correct for creatinine.  Diurnal variation in urine markers ```

Answer 12

``` ALKALINE PHOSPHATASE (ALP) • Formation Marker ``` Used in the diagnosis/monitoring of: • Pagets • Osteomalacia • Bone metastasis

Answer 13

BSAP – Bone-Specific Alkaline Phosphatase: • Types – tissue-specific (bone) form of ALP. • Roles – essential for mineralisation of bone & regulates concentrations of phosphate. • Uses – T1/2 40 hours. Increased in Paget’s, osteomalacia, bone metastasis, HPT, HT.  NOTE that ALP varies with age (younger people have more)

Answer 14

As predictor of response to anabolic treatments | • e.g. PTH treatment

Answer 15

Chronic Kidney Disease: o Skeletal remodelling disorders caused by CKD contribute to vascular calcification (extra-skeletal deposition) o The disorders in mineral metabolism with CKD are a main reason to mortality from CKD Pathophysiology: – impairs skeletal anabolism – decreases osteoblast function – decreases bone formation.

Answer 16

Biochemistry: – increased [phosphate] – reduced calcitriol  Think, kidney failure so less calcitriol and nephron loss so less phosphate filtrated into urine Pathway: – 2o HPT develops to compensate --> unsuccessful so hypocalcaemia --> parathyroid become autonomous (tertiary hyperparathyroidism) --> hypercalcaemia There is a progressive hyperplasia of the parathyroids

Answer 17

(1) Phosphate binds to Ca in serum • Calcium phosphate crystals are deposited causing extra-skeletal calcifications (2) Acidosis • causes demineralisation (3) Decreased calcitriol • leads to hypocalcaemia = 2o PTH = increased bone resorption • also leads to osteomalacia (problem w. mineralisation)

Answer 18

Heterotropic calcification • bone formation at an abnormal anatomical site, usually in soft tissue • i.e. in MCP joints

Answer 19

Renal osteodystrophy is a CONSEQUENCE of CKD! The results of CKD cause the symptoms of osteodystrophy such as heterotopic calcification.